Neutralizing Monoclonal Antibodies That Target the Spike Receptor Binding Domain Confer Fc Receptor-Independent Protection against SARS-CoV-2 Infection in Syrian Hamsters

Su, Wen; Sia, Sin Fun; Schmitz, Aaron J.; Bricker, Traci L.; Starr, Tyler N; Greaney, Allison J; Turner, Jackson S.; Mohammed, Bassem M.; Liu, Zhuoming; Choy, Ka Tim; Joshi, Astha; Cheng, Ka Man; Wong, Alvina Y L; Harastani, Houda H.; Nicholls, John M.; Whelan, Sean P. J.; Bloom, Jesse D; Yen, Hui‐Ling; Ellebedy, Ali H.; Boon, Adrianus C. M.

doi:10.1128/mbio.02395-21

Cited by 20 publications

(16 citation statements)

References 37 publications

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“…These time points for necropsies and tissue collections were based on optimized ones that were established in the Boon and Diamond laboratories. 19 , 21 , 22 , 24 , 41 , 42 These time points coincided with maximal infection, pathological findings, and weight loss. The left lobe was homogenized in 1.0 mL of Dulbecco’s Modified Eagle Medium (DMEM), clarified by centrifugation (1,000 x g for 5 min) and used for viral titer analysis by quantitative RT-PCR (RT-qPCR) using primers and probes targeting the N gene, and by plaque assay.…”

Section: Methodsmentioning

confidence: 65%

“…Syrian hamsters are naturally susceptible to SARS-CoV-2 and considered an excellent model for COVID-19. 19 , 21 , 22 , 23 , 24 Groups of 5- to 6-week-old male hamsters were immunized once with the 10 8 or 10 10 dose of the Ad26.COV2.S vaccine ( Figure 4 A). Serum was collected 21 days later, and antibody responses were evaluated by ELISA and FRNT.…”

Section: Resultsmentioning

confidence: 99%

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mRNA-1273 and Ad26.COV2.S vaccines protect against the B.1.621 variant of SARS-CoV-2

Bai

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VanBlargan

et al. 2022

Med

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Section: Methodsmentioning

confidence: 65%

Section: Resultsmentioning

confidence: 99%

mRNA-1273 and Ad26.COV2.S vaccines protect against the B.1.621 variant of SARS-CoV-2

Bai

Whitener

VanBlargan

et al. 2022

Med

Self Cite

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“…First, we deleted nucleotides 2-42 of the SARS-CoV-2 s2m (CoV-2-s2m Δ2-42 ) as the s2m is completely encoded in the 3′ UTR (Table S1). We also created a mutant that contained four consecutive nucleotide substitutions in the stem region of the s2m (CoV-2-s2m [2][3][4][5] ) that is predicted to disrupt the secondary structure as well as a revertant mutant (CoV-2-s2m [2][3][4][5][39][40][41][42] ) that contained four additional compensatory substitutions that restored the predicted stem region and the SARS-CoV-2 s2m secondary structure (Table S1, Fig. S3).…”

Section: -S2)mentioning

confidence: 99%

The highly conserved stem-loop II motif is important for the lifecycle of astroviruses but dispensable for SARS-CoV-2

Janowski

Jiang

Fujii

et al. 2022

Preprint

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The stem-loop II motif (s2m) is an RNA element present in viruses from divergent viral families, including astroviruses and coronaviruses, but its functional significance is unknown. We created deletions or substitutions of the s2m in astrovirus VA1 (VA1), classic human astrovirus 1 (HAstV1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For VA1, recombinant virus could not be rescued upon partial deletion of the s2m or substitutions of G-C base pairs. Compensatory substitutions that restored the G-C base-pair enabled recovery of VA1. For HAstV1, a partial deletion of the s2m resulted in decreased viral titers compared to wild-type virus, and reduced activity in a replicon system. In contrast, deletion or mutation of the SARS-CoV-2 s2m had no effect on the ability to rescue the virus, growth in vitro, or growth in Syrian hamsters. Our study demonstrates the importance of the s2m is virus-dependent.

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“…Another effective way is the neutralizing monoclonal antibodies (mAbs) at present ( Renn et al, 2020 ). However, the production of safe and effective mAbs is complicated, and the duration of effective protection remains to be determined ( Su et al, 2021 ; Taylor et al, 2021 ). Moreover, continuous mutations of SARS-CoV-2 during the pandemic may cause coronavirus to escape from antibody recognition and reduce the neutralizing activity of mAbs ( Du et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Tuftsin: A Natural Molecule Against SARS-CoV-2 Infection

Huang

Wang

et al. 2022

Front. Mol. Biosci.

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Coronavirus disease 2019 (COVID-19) continuously progresses despite the application of a variety of vaccines. Therefore, it is still imperative to find effective ways for treating COVID-19. Recent studies indicate that NRP1, an important receptor of the natural peptide tuftsin (released from IgG), facilitates SARS-CoV-2 infection. Here, we found 91 overlapping genes between tuftsin targets and COVID-19-associated genes. We have demonstrated that tuftsin could also target ACE2 and exert some immune-related functions. Molecular docking results revealed that tustin could combine with ACE2 and NRP1 in stable structures, and their interacted regions cover the binding surfaces of S1-protein with the two receptors. Using surface plasmon resonance (SPR) analysis, we confirmed that tuftsin can bind ACE2 and NRP1 directly. Importantly, using SPR-based competition assay we have shown here that tuftsin effectively prevented the binding of SARS-CoV-2 S1-protein to ACE2. Collectively, these data suggest that tuftsin is an attractive therapeutic candidate against COVID-19 and can be considered for translational as well as clinical studies.

show abstract

Neutralizing Monoclonal Antibodies That Target the Spike Receptor Binding Domain Confer Fc Receptor-Independent Protection against SARS-CoV-2 Infection in Syrian Hamsters

Cited by 20 publications

References 37 publications

mRNA-1273 and Ad26.COV2.S vaccines protect against the B.1.621 variant of SARS-CoV-2

mRNA-1273 and Ad26.COV2.S vaccines protect against the B.1.621 variant of SARS-CoV-2

The highly conserved stem-loop II motif is important for the lifecycle of astroviruses but dispensable for SARS-CoV-2

Tuftsin: A Natural Molecule Against SARS-CoV-2 Infection

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